1. (Salen)Mn(III) Compound as a Nonpeptidyl mimic of Catalase Catalase 2H 2 O 2 2H 2 O + O 2 An incomplete list of possible treatment applications: Alzheimer’s disease Stroke Heart disease Aging Cancer (reduction of the side effects, allowing higher drug doses to be administered) Substituents change enzymatic activity: the biomimetic can be tuned structurally and electronically Intelligent design of Biomimetics (Synzymes):

2. RAS GAP GTP

3. ~ 40 Å QM part: 45 atoms MM part: 1608 atoms collected in 483 EFs

4. Potential energy surface for the GTP hydrolysis for the RAS/GAP complex model (calculated at the B3LYP/4-31G*/3-21G level)  E(kcal/mol) R[O(W)-P  ] R[P  -O(P  )] Reaction path

6. Characterization of Ping-Pong Mechanism for Dismutation of H 2 O 2 Molecule by (Salen)Mn(III)

7. Mechanism-Based Structural Tuning of Catalase Activity of Salen-Manganese Complexes for R=OMe substituted compound Abashkin, Burt Inorg. Chem., 2005; Abashkin, Burt Phys. Chem. B, 2004 Estimated computer resources needed for the exhaustive tuning : 50-60 (substituted biomimetics) x 200-400 (hours of large CPU) = YEARS Dramatic increase in computation power is needed to solve the problem

8. Computational assistance in developing novel biological nanodevices: Target DNA/RNA Target “Simple” Nanoprobe for detecting biowarfare reagents and genetic diseases. Red light Fluorescein Green Light Recognizer

9. Practical development of Nanoprobe needs optimization of various elements: Target Rod Polyethylenglycol (PEG) tether Recognizer Linker Fluorophores Computational support includes QM ( hundreds of atoms) and MM (thousands of atoms) calculations and/or complex QM/MM simulations Feasible only on a supercomputer

10. Epidermal Growth Factor Receptor Pathway

11. Dendrimers

12. Large number of micro-environments with different properties

13. Gold Nanoparticles

14. Buckyball (left) 500 atoms 3000 electrons Gold Particle 3000 to 30000 atoms 500,000 electrons Problem grows as Ne 2